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TGF-β応答性FOX C-1遺伝子の機能解析及びそのシグナル伝達路の同定

Research Project

Project/Area Number 14657425
Research Category

Grant-in-Aid for Exploratory Research

Allocation TypeSingle-year Grants
Research Field Obstetrics and gynecology
Research InstitutionKyushu University

Principal Investigator

和氣 徳夫  九州大学, 生体防御医学研究所, 教授 (50158606)

Co-Investigator(Kenkyū-buntansha) 松田 貴雄  九州大学, 大学病院, 助手 (10304825)
加藤 聖子  九州大学, 生体防御医学研究所, 講師 (10253527)
加藤 秀則  九州大学, 大学病院, 講師 (60214392)
有馬 隆博  九州大学, 生体防御医学研究所, 助手 (80253532)
Project Period (FY) 2002 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2003: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2002: ¥2,100,000 (Direct Cost: ¥2,100,000)
KeywordsFOX C1 / forkhead transcription factor / TGF-β1 responsive / somatic mutation / transcriptional silencing / tumor suppressor gene / Microallay analysis
Research Abstract

FOX C-1下流シグナル
TGF-βは様々なメカニズムを介して細胞増殖を調節している。FOX C-1はその一部のシグナルを構成すると考えられる。私たちはF0X C-1遺伝子導入HeLa細胞を用い、TGF-βによるFOX C-1下流シグナルについて検討した。HeLa親細胞、FOX C-1遺伝子導入HeLa細胞を用い、抗Rb抗体を用いたウエスタンブロットを施行したところ、両細胞共にRb蛋白の発現は認められなかった。さらにTGF-β1によるRb蛋白発現さらには、脱リン酸化型へのシフトも観察されなかった。さらにRb蛋白のリン酸化を抑制するp27/KIP、p15/INK4B、p21/CIP1などのCDKインヒビター発現についても検討した。FOX C-1遺伝子導入HeLa細胞は、TGF-β1による有意な細胞増殖抑制を示すが、これらのCDKインヒビターはTGF-β1に応答し、発現亢進を示すことはなかった。以上からFOX C-1蛋白はTGF-βの下流でRb蛋白を介する経路とは異なるシグナル伝達により、細胞増殖を負に制御することが示唆された。このため、FOX C-1強制発現HeLa細胞と親細胞の間で、TGF-β1存在下及び非存在下におけるマイクロアレイ法を用いた大容量遺伝子発現変化の解析をおこなった。その結果、29遺伝子がF0X C-1強制発現に伴い、発現亢進し、21遺伝子が発現抑制を受けていることが判明した。現在、これら遺伝子群の詳細な機能を解析し、FOX C-1下流シグナル伝達路を明らかにする研究を進めている。

Report

(2 results)
  • 2003 Annual Research Report
  • 2002 Annual Research Report
  • Research Products

    (13 results)

All Other

All Publications (13 results)

  • [Publications] Asanoma K et al.: "NECC1, a candidate choriocarcinoma suppressor gene which encodes homeodomain consensus motif."Genomics. 81. 15-25 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ueoka Y et al.: "Hepatocyte growth factor modulates motility and invasiveness of ovarian carcinomas via Ras mediated pathway."Molecular and cellular endocrinology. 202. 80-88 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Yamayoshi A et al.: "Photodynamic antisense therapy : regulation of cervical carcinoma cells by psoralen-conjugated oligonucleotides."Nucleic Acid Research Supplement. 3. 75-76 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Matsuda T et al.: "Genetics and molecular markers in gestational trophoblastic disease with special reference to their clinical application."Best Practice & Research Clinical Obstetrics and Gynecology. 17. 827-836 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Oudejans CBM et al.: "The parent - of - origin effect of 10q22 coincides with two regions enriched for genes with downregulated expression in androgenetic placenta"Hum Mol Genet. (in press). (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ninomiya et al.: "K-Ras and H-Ras activation promote distinct consequences on endometrial c11 survival."Cancer Reserch. (in press). (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kato K et al.: "Cell and Molecular Biology of Endometrial Carcinoma : Contribution of estrogen receptor α and progesterone receptor-β to oncogenic K-Ras-mediated NIH3T3 cell transformation."Springer-verlag Tokyo 2003. 207-218 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kato K et al.: "Contribution of estrogen receptors (ERα) to oncogenic K-Ras-mediated NIH3T3 cell transformation and its implication for escape from senescence by modulating the p53 pathway"Journal of Biological Chemistry. 277. 11217-11224 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kato H et al.: "Growth-associated Gene Expression Profiles by Microarray Analysis of Trophoblast of Molar Pregnancies and Normal Villi"International Journal of Gynecological Pathology. 21.3. 255-260 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Zhou Y et al.: "Identification of FOXC1 as a TGF-β1 responsive gene and its involvement in negative regulation of cell growth"Genomics. 80.5. 465-472 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Asanoma K et al.: "NECC1, a candidate choriocarcinoma suppressor gene which encodes homeodomain consensus motif"Geonomics. (in press).

    • Related Report
      2002 Annual Research Report
  • [Publications] Ueoka Y et al.: "Hepatocyte growth factor modulates motility and invasiveness of ovarian carcinoma via Ras mediated pathway"Molecular and cellular endocrinology. (in press).

    • Related Report
      2002 Annual Research Report
  • [Publications] Kato K et al.: "Cell and Molecular Biology of Endometrial Carcinoma, Springer-Verlag Tokyo"Contribution of estrogen receptor α and progesterone receptor-B to oncogenic K-Ras-mediated NIH3T3 cell transformation(in press).

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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